Studies were continued this year to determine how growth hormone (GH) secretion is regulated from puberty through adulthood and how the GH axis, particularly insulin like growth factor-I (IGF-I), affects reproductive maturation and fertility. Gonadally-intact and ovariectomized, estradiol (E2) treated adolescent and adult females supplemented with human IGF-I (given SC) were compared to unsupplemented cohorts. For adult females, IGF-I diminished the response in serum GH to GH-releasing hormone (GHRH); however, this effect was reversed by pretreatment with E2. E2 enhanced the response to GHRH, either by increasing the releasable pools of GH from the pituitary somatotrophs, sensitizing the pituitary to GHRH, or acting on GHRH neurons in the hypothalamus. Since the response in GH to stimulation with NMDA, a glutamate agonist, was similar regardless of IGF-I or E2 treatment, IGF-I and E2 may indeed affect GHRH at the level of the neuron. IGF-I also diminished the response i n GH to GHRH stimulation in adolescent females throughout maturation. Again, E2 enhanced the response to GHRH, even in the presence of IGF-I. NMDA activated the GHRH neuron similarly between untreated and IGF-I supplemented and/or E2 treated females, as assessed by the response in GH. Consequently, it appears that the regulation of GH secretion by IGF-I and E2 is at the level of the GHRH neuron. Studies continued during this year to determine if IGF-I affects the tempo of puberty and whether IGF-I regulates of LH and ovarian steroid secretion in adults. The negative feedback effectiveness of three doses of E2 on LH secretion in ovariectomized adults was not affected by IGF-I. Furthermore, the response in serum LH to NMDA administration was similar between control and IGF-I treated females under all E2 treatment conditions. In contrast, IGF-I administration decreased the hypersensitivity to E2 negative feedback inhibition in adolescent females. These data suggest that IGF-I may, in part, influence developmental increases in gonadotropin secretion. Indeed, first ovulation appears to be advanced by IGF-I administration, due to shortening the interval between menarche and first ovulation - a period characterized by hypersensitivity to E2 negative feedback. These studies will not only provide a better understanding of how GH is regulated throughout adulthood, helping to provide treatment strategies for individuals with aberrations in GH secretion, but will also more fully define what variables affect reproductive maturation and fertility in women.